The purpose of this project is to establish the chemopreventive potential of supplementation with the essential trace element Selenium (Se). This chemoprevention research project has the opportunity to conclusively demonstrate the cancer prevention potential of Se supplementation in a randomized double-blind primary cancer prevention trial conducted in the low forage Se region of the U.S. Because the majority of the U.S. population lives in relatively low-Se areas (where the trial's clinics are located), the public health implications of this project's results are very relevant and significant. The results of this trial are directly generalizable to those individuals with a history of non-melanoma skin cancer; they may also be relevant for other populations, especially individuals at elevated risk for other cancers. This study can provide the initial evidence that Sc supplementation has the potential to decrease both mortality from all causes of death and cancer as well as the incidence of cancers. This study is a double-blind, placebo controlled phase III cancer prevention trial in a population at high risk of non-melanoma skin cancer, using a single nutrient to test the primary trial hypothesis that Se supplementation reduces cancer incidence and mortality. The population is free-living and essentially healthy (except for a history of non-melanoma skin cancer) and attends one of seven dermatology clinics in the low forage Se area of the eastern coastal plain of the U.S. The trial will utilize 200 mcg. and 400 mcg. doses of Sc as well as a placebo. Existing patients that are on the 200 mcg. supplement will be maintained at that dose and new patients will be randomized to the 400 mcg. dose. The 400 mcg. dose allows for excellent separation of plasma Se levels between the treatment and placebo groups and enhances the statistical power of the trial. The trial's external Safety Monitoring and Advisory Committee has recommended that the specific aims be expanded to the health endpoints of cancer incidence and mortality. Therefore, the specific aims are related to three issues: cancer incidence, mortality, and cancer screening. The specific aims related to cancer incidence are: to demonstrate that, compared to the placebo, Se supplementation will significantly reduce the incidence of non-melanoma skin cancer (specifically squamous cell carcinoma of the skin), that of all cancer sites combined (except non- melanoma skin cancer), the site-specific incidence of lung, prostate, and colorectal cancer, and the incidence of preneoplastic disease, specifically colorectal adenomatous polyps. Those related to mortality are to demonstrate that Se supplementation reduces mortality from all causes of death combined and from all cancers combined (specifically lung cancer). The specific aim related to cancer screening is to implement cancer screening protocols, specifically for colon cancer and prostate specific antigen. Additional aims are to evaluate higher doses of Se supplementation and to establish the long term safety of Se supplementation.